Baseline Neutrophil-To-Lymphocyte Ratio as a Risk Stratification Marker for Severe Checkpoint Inhibitor Pneumonitis...

Severe checkpoint inhibitor pneumonitis (CIP), particularly when it develops within 6-12 weeks, is a potentially fatal adverse event in patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Although neutrophil-to-lymphocyte ratio (NLR) has been reported to predict immune-related adverse events, its role in severe CIP remains unclear.

The discovery cohort retrospectively enrolled 102 patients with NSCLC treated with ICI monotherapy at Hiroshima University Hospital. The validation cohort prospectively enrolled 191 NSCLC patients receiving first-line treatment, including ICI, at 15 institutions. Severe CIP was defined as grade 3-5 pneumonitis occurring within 3 months of treatment initiation. The cut-off level of the baseline NLR was identified by receiver operating characteristic curve analysis in the discovery cohort, and the predictive accuracy was analyzed and confirmed in both cohorts.

Severe CIP was observed in seven (6.9%) and 11 (5.8%) patients in the discovery and validation cohorts, respectively. In the discovery cohort, the baseline NLR was higher in patients with severe CIP than in those without (17.29 [4.76-20.73] vs. 3.70 [2.64-6.68], p = 0.006), and the cut-off level of the baseline NLR was set at 4.75 (AUC 0.81; sensitivity 85.7%, specificity 64.2%). The incidence of severe CIP was significantly higher in patients with higher baseline NLR levels (≥ 4.75) than in those without, in both cohorts (discovery: 15.0% vs. 1.6%, p = 0.009; validation: 10.3% vs. 3.3%, p = 0.046).

Baseline NLR is a promising risk stratification marker for severe CIP.